The overall goal of this proposal is to elucidate the mechanisms(s) which control the expression of streptococcal adhesins at the molecular level. Streptococcus mutans is the principal causative agent of human dental cavities, and is among the primary colonizers of the oral cavity. Owing to its ability to adhere tenaciously to the tooth surface, S. mutans initiates the formation of dental plaque which, in turn, provides a substrate for the subsequent accretion of other oral pathogens. Data from several laboratories strongly suggest that adhesion of the pathogenic streptococci to in vitro models of the tooth surface is mediated by multiple adhesins. Not surprisingly, successful pathogens generally exhibit multiple adhesion mechanisms to ensure their ability to colonize host tissues. The expression of streptococcal adhesins may therefore involve the coordinate expression of several genes required for bacterial adhesion. The applicant's laboratory has recently identified a novel locus on the S. mutans chromosome, adh. which putatively controls the expression of multiple adhesins. Thus, the application proposes to: (1) clone the S. mutans adh locus; (2) sequence adh to reveal its structural organization; (3) construct an adh deletion mutant to confirm a role for adh in S. mutans adhesion; (4) characterize the putative gene product(s) of S. mutans adh; and (5) monitor the expression of adh in planktonic and adherent S. mutans cells. Indeed, the involvement of adh in modulating the composition of the S. mutans cell surface needs to be further investigated. Such investigations will contribute to the field of bacterial adhesion in the oral environment as well as to our basic understanding of the genetics of streptococci. Moreover, this research could identify adh and its putative gene product(s) as a target for the development of anti-plaque reagents and/or anti-caries vaccine.